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Treatment with Parathyroid Hormone hPTH(1-34), hPTH(1-31), and Monocyclic hPTH(1-31) Enhances Fracture Strength and Callus Amount After Withdrawal Fracture Strength and Callus Mechanical Quality Continue to Increase

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Abstract

The influence of intermittent hPTH(l-34)NH2, hPTH(1-31)NH2, and monocyclic [Leu27]cyclo(Glu22-Lys26)hPTH(1-31)NH2 treatment on callus formation, mechanical strength, and callus tissue mechanical quality of tibial fractures in rats was investigated after 8 and 16 weeks of healing. In the 8 weeks of healing animals, the PTH-peptides were injected subcutaneously during the entire observation period (15 nmol/kg/day [hPTH(1-34)NH2: 15 nmol = 60 µg]), and control animals with fractures were given vehicle. In the 16 weeks of healing animals, the PTH-peptides were injected only during the first 8 weeks of healing (15 nmol/kg/day), after which the animals were left untreated during the rest of the healing period. After the first 8 weeks of healing, increased fracture strength and callus volume were seen in the PTH-treated rats (ultimate load 66%, ultimate stiffness 58%, callus volume 28%), and the three peptides were equally effective. No difference in callus tissue mechanical quality was found between PTH and vehicle animals. After 16 weeks of healing, no differences in fracture strength, callus volume, or callus tissue mechanical quality were seen between PTH and vehicle. When comparing PTH-treated animals at 8 and 16 weeks, fracture strength and callus tissue mechanical quality continued to increase after the withdrawal of PTH (ultimate load 23%, ultimate stress 88%, elastic modulus 87%) and external callus volume declined during this period (27%).

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References

  1. V Shen DW Dempster RWE Mellish R Birchman W Horbert R Lindsay (1992) ArticleTitleEffects of combined and separate intermittent administration of low-dose human parathyroid hormone fragment (1–34) and 17β-estradiol on bone histomorphometry in ovariectomized rats with established osteopenia. Calcif Tissue Int 50 214–220 Occurrence Handle1:CAS:528:DyaK38XktVWnsLk%3D Occurrence Handle1617495

    CAS  PubMed  Google Scholar 

  2. H Oxlund C Ejersted TT Andreassen O Tørring MHL Nilsson (1993) ArticleTitleParathyroid hormone (1–34) and (1–84) stimulate cortical bone formation both from periosteum and endosteum. Calcif Tissue Int 53 394–399

    Google Scholar 

  3. TJ Wronski C-F Yen H Qi LM Dann (1993) ArticleTitleParathyroid hormone is more effective than estrogen or bisphosphonates for restoration of lost bone mass in ovariectomized rats. Endocrinology 132 823–831

    Google Scholar 

  4. L Mosekilde CC Danielsen J Gasser (1994) ArticleTitleThe effect on vertebral bone mass and strength of long-term treatment with antiresorptive agents (estrogen and calcitonin), human parathyroid hormone-(1-38), and combination therapy, assessed in aged ovariectomized rats. Endocrinology 134 2126–2134

    Google Scholar 

  5. C Ejersted TT Andreassen MHL Nilsson H Oxlund (1994) ArticleTitleHuman parathyroid hormone (1–34) increases bone formation and strength of cortical bone in aged rats. Eur J Endocrinol 130 201–207

    Google Scholar 

  6. L Mosekilde CC Danielsen CH Søgaard JE McOsker TJ Wronski (1995) ArticleTitleThe anabolic effects of parathyroid hormone on cortical bone mass, dimensions and strength - assessed in a sexually mature, ovariectomized rat model. Bone 16 223–230 Occurrence Handle10.1016/8756-3282(94)00033-V Occurrence Handle1:CAS:528:DyaK2MXltlCrtb4%3D Occurrence Handle7756051

    Article  CAS  PubMed  Google Scholar 

  7. H Dobnig RT Turner (1995) ArticleTitleEvidence that intermittent treatment with parathyroid hormone increases bone formation in adult rats by activation of bone lining cells. Endocrinology 136 3632–3638

    Google Scholar 

  8. JF Whitfield P Morley G Willick S Maclean V Ross RJ Isaacs J-R Barbier (1998) ArticleTitleComparison of the abilities of human parathyroid hormone (hPTH)-(1-34) and [Leu27]-cyclo(Glu22-Lys26)-hPTH-(1-31)NH2 to stimulate femoral trabecular bone growth in ovariectomized rats. Calcif Tissue Int 63 423–428 Occurrence Handle10.1007/s002239900551 Occurrence Handle1:CAS:528:DyaK1cXntV2qu7k%3D Occurrence Handle9799828

    Article  CAS  PubMed  Google Scholar 

  9. TT Andreassen H Oxlund (2000) ArticleTitleThe influence of combined parathyroid hormone and growth hormone treatment on cortical bone in aged ovariectomized rats. J Bone Miner Res 15 2266–2275

    Google Scholar 

  10. C Ejersted TT Andreassen H Oxlund PH Jørgensen B Bak J Häggblad O Tørring MHL Nilsson (1993) ArticleTitleHuman parathyroid hormone (1-34) and (1-84) increase the mechanical strength and thickness of cortical bone in rats. J Bone Miner Res 8 1097–1101 Occurrence Handle1:CAS:528:DyaK2cXjtFKgt7w%3D Occurrence Handle8237479

    CAS  PubMed  Google Scholar 

  11. M Sato GQ Zeng CH Turner (1997) ArticleTitleBiosynthetic human parathyroid hormone (1-34) effects on bone quality in aged ovariectomized rats. Endocrinology 138 4330–4337 Occurrence Handle1:CAS:528:DyaK2sXmsVWmsbY%3D Occurrence Handle9322947

    CAS  PubMed  Google Scholar 

  12. C Ejersted H Oxlund EF Eriksen TT Andreassen (1998) ArticleTitleWithdrawal of parathyroid hormone treatment causes rapid resorption of newly formed vertebral cancellous and endocortical bone in old rats. Bone 23 43–52 Occurrence Handle10.1016/S8756-3282(98)00072-6 Occurrence Handle1:CAS:528:DyaK1cXksVygs7c%3D Occurrence Handle9662129

    Article  CAS  PubMed  Google Scholar 

  13. V Shen R Birchman XG Liang DD Wu DW Dempster R Lindsay (1998) ArticleTitleAccretion of bone mass and strength with parathyroid hormone prior to the onset of estrogen deficiency can provide temporary beneficial effects in skeletally mature rats. J Bone Miner Res 13 883–890

    Google Scholar 

  14. P Morley JF Whitfield GE Willick V Ross S Maclean J-R Barbier RJ Isaacs TT Andreassen (2001) ArticleTitleThe effect of monocyclic and bicyclic analogs of human parathyroid hormone (hPTH)-(1-31)NH2 on bone formation and mechanical strength in ovariectomized rats. Calcif Tissue Int 68 95–101 Occurrence Handle1:CAS:528:DC%2BD3MXkvFersr8%3D Occurrence Handle11310353

    CAS  PubMed  Google Scholar 

  15. N Yamamoto HE Takahashi T Tanizawa R Fujimoto T Hara S Tanaka (1993) ArticleTitleMaintenance of bone mass by physical exercise after discontinuation of intermittent hPTH(1-34) administration. Bone Miner 23 333–342

    Google Scholar 

  16. Y Takano T Tanizawa T Mashiba N Endo S Nishida HE Takahashi (1996) ArticleTitleMaintaining bone mass by bisphosphonate incadronate disodium (YM175) sequential treatment after discontinuation of intermittent human parathyroid hormone (1-34) administration in ovariectomized rats. J Bone Miner Res 11 169–177

    Google Scholar 

  17. C Ejersted H Oxlund TT Andreassen (1998) ArticleTitleBisphosphonate maintains parathyroid hormone (1-34)-induced cortical bone mass and mechanical competence in old rats. Calcif Tissue Int 62 316–322 Occurrence Handle10.1007/s002239900438 Occurrence Handle1:CAS:528:DyaK1cXhvFynu74%3D Occurrence Handle9504956

    Article  CAS  PubMed  Google Scholar 

  18. TT Andreassen C Ejersted H Oxlund (1999) ArticleTitleIntermittent parathyroid hormone (1-34) treatment increases callus formation and mechanical strength of healing rat fractures. J Bone Miner Res 14 960–968

    Google Scholar 

  19. G Holzer RJ Majeska MW Lundy JR Hartke TA Einhorn (1999) ArticleTitleParathyroid hormone enhances fracture healing. A preliminary report. Clin Orthop 366 258–263 Occurrence Handle10.1097/00003086-199909000-00033 Occurrence Handle10627743

    Article  PubMed  Google Scholar 

  20. JS Jahng HW Kim (2000) ArticleTitleEffect of intermittent administration of parathyroid hormone on fracture healing in ovariectomized rats. Orthopedics 23 1089–1094 Occurrence Handle1:STN:280:DC%2BD3crgtVWkuw%3D%3D Occurrence Handle11045557

    CAS  PubMed  Google Scholar 

  21. TT Andreassen C Fledelius C Ejersted H Oxlund (2001) ArticleTitleIncreases in callus formation and mechanical strength of healing fractures in old rats treated with parathyroid hormone. Acta Orthop Scand 72 304–307 Occurrence Handle10.1080/00016470152846673 Occurrence Handle1:STN:280:DC%2BD3MvjtlCjsA%3D%3D Occurrence Handle11480610

    Article  CAS  PubMed  Google Scholar 

  22. A Nakajima N Shimoji K Shiomi S Shimizu H Moriya TA Einhorn M Yamazaki (2002) ArticleTitleMechanisms for the enhancement of fracture healing in rats treated with intermittent low-dose human parathyroid hormone (1–34). J Bone Miner Res 17 2038–2047 Occurrence Handle1:CAS:528:DC%2BD38Xoslems7k%3D Occurrence Handle12412812

    CAS  PubMed  Google Scholar 

  23. J-R Barbier W Neugebauer P Morley V Ross M Soska JF Whitfield G Willick (1997) ArticleTitleBioactivities and secondary structures of constrained analogues of human parathyroid hormone: cyclic lactams of the receptor binding region. J Med Chem 40 1373–1380 Occurrence Handle10.1021/jm960743o Occurrence Handle1:CAS:528:DyaK2sXitlWjsL8%3D Occurrence Handle9135034

    Article  CAS  PubMed  Google Scholar 

  24. CH Turner DB Burr (1993) ArticleTitleBasic biomechanical measurement of bone: a tutorial. Bone 14 595–608 Occurrence Handle1:STN:280:ByuC3c%2FgtVw%3D Occurrence Handle8274302

    CAS  PubMed  Google Scholar 

  25. PH Jørgensen B Bak TT Andreassen (1991) ArticleTitleMechanical properties and biochemical composition of rat cortical femur and tibia after long-term treatment with biosynthetic human growth hormone. Bone 12 353–359 Occurrence Handle1:STN:280:By2C2cvivVc%3D Occurrence Handle1782103

    CAS  PubMed  Google Scholar 

  26. B Bak PH Jørgensen TT Andreassen (1991) ArticleTitleThe stimulating effect of growth hormone on fracture healing is dependent on onset and duration of administration. Clin Orthop 264 295–301 Occurrence Handle1997248

    PubMed  Google Scholar 

  27. LJ Fraher R Avram PH Watson GN Hendy JE Henderson KL Chong D Goltzman P Morley GE Willick JF Whitfield AB Hodsman (1999) ArticleTitleComparison of the biochemical responses to human parathyroid hormone-(1-31)NH2 and hPTH-(1-34) in healthy humans. J Clin Endocrinol Metab 84 2739–2743 Occurrence Handle1:CAS:528:DyaK1MXltFCltr0%3D Occurrence Handle10443671

    CAS  PubMed  Google Scholar 

  28. S Mohan S Kutilek C Zhang HG Shen Y Kodama AK Srivastava JE Wergedal WG Beamer DJ Baylink (2000) ArticleTitleComparison of bone formation responses to parathyroid hormone (1-34), (1-31), and (2-34) in mice. Bone 27 471–478 Occurrence Handle10.1016/S8756-3282(00)00355-0 Occurrence Handle1:CAS:528:DC%2BD3cXnt1Sjtrs%3D Occurrence Handle11033441

    Article  CAS  PubMed  Google Scholar 

  29. MPG Bostrom SC Gamradt P Asnis BH Vickery E Hill Z Avnur RV Waters (2000) ArticleTitleParathyroid hormone-related protein analog RS-66271 is an effective therapy for impaired bone healing in rabbits on corticosteroid therapy. Bone 26 437–442 Occurrence Handle10.1016/S8756-3282(00)00251-9 Occurrence Handle1:CAS:528:DC%2BD3cXisFGrur0%3D Occurrence Handle10773582

    Article  CAS  PubMed  Google Scholar 

  30. R Skripitz TT Andreassen P Aspenberg (2000) ArticleTitleParathyroid hormone (1-34) increases the density of rat cancellous bone in a bone chamber. J Bone Joint Surg Br 82-B 138–141

    Google Scholar 

  31. R Skripitz TT Andreassen P Aspenberg (2000) ArticleTitleStrong effect of PTH (1-34) on regenerating bone: a time sequence study in rats. Acta Orthop Scand 71 619–624 Occurrence Handle10.1080/000164700317362271 Occurrence Handle1:STN:280:DC%2BD3M%2Fos1GlsA%3D%3D Occurrence Handle11145391

    Article  CAS  PubMed  Google Scholar 

  32. R Skripitz P Aspenberg (2001) ArticleTitleImplant fixation enhanced by intermittent treatment with parathyroid hormone. J Bone Joint Surg Br 83-B 437–440 Occurrence Handle10.1302/0301-620X.83B3.10256

    Article  Google Scholar 

  33. R Skripitz P Aspenberg (2001) ArticleTitleEarly effect of parathyroid hormone (1-34) on implant fixation. Clin Orthop 292 IssueID392 427–432

    Google Scholar 

  34. R Lindsay J Nieves C Formica E Henneman L Woelfert V Shen D Dempster F Cosman (1997) ArticleTitleRandomised controlled study of effect of parathyroid hormone on vertebral-bone mass and fracture incidence among postmenopausal women on oestrogen with osteoporosis. Lancet 350 550–555 Occurrence Handle1:CAS:528:DyaK2sXlvVamsb0%3D Occurrence Handle9284777

    CAS  PubMed  Google Scholar 

  35. RS Rittmaster M Bolognese MP Ettinger DA Hanley AB Hodsman DL Kendler CJ Rosen (2000) ArticleTitleEnhancement of bone mass in osteoporotic women with parathyroid hormone followed by alendronate. J Clin Endocrinol Metab 85 2129–2134 Occurrence Handle1:CAS:528:DC%2BD3cXlsVequr0%3D Occurrence Handle10852440

    CAS  PubMed  Google Scholar 

  36. RM Neer CD Arnaud JR Zanchetta R Prince GA Gaich J-Y Reginster AB Hodsman EF Eriksen S Ish-Shalom HK Genant O Wang BH Mitlak (2001) ArticleTitleEffect of parathyroid hormone (1-34) on fractures and bone mineral densizty in postmenopausal women with osteoporosis. N Engl J Med 344 1434–1441 Occurrence Handle1:CAS:528:DC%2BD3MXktVSgsbw%3D Occurrence Handle11346808

    CAS  PubMed  Google Scholar 

  37. ES Orwoll WH Scheele S Paul S Adami U Syversen A Diez-Perez J-M Kaufman AD Clancy GA Gaich (2003) ArticleTitleThe effect of teriparatide [human parathyroid hormone (1-34)] therapy on bone density in men with osteoporosis. J Bone Miner Res 18 9–17 Occurrence Handle1:CAS:528:DC%2BD3sXltFKmtw%3D%3D Occurrence Handle12510800

    CAS  PubMed  Google Scholar 

  38. R Marcus O Wang J Satterwhite B Mitlak (2003) ArticleTitleThe skeletal response to teriparatide is largely independent of age, initial bone mineral density, and prevalent vertebral fractures in postmenopausal women with osteoporosis. J Bone Miner Res 18 18–23 Occurrence Handle1:CAS:528:DC%2BD3sXltFKmtQ%3D%3D Occurrence Handle12510801

    CAS  PubMed  Google Scholar 

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Acknowledgements

We are grateful to M. Fischer and J. Utoft for excellent technical assistance.

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Authors and Affiliations

  1. Department of Connective Tissue Biology, Institute of Anatomy, University of Aarhus, Aarhus, Denmark

    T. T. Andreassen

  2. Institute for Biological Science, National Research Council of Canada, Ottawa, Ontario, Canada

    G. E. Willick, P. Morley & J. F. Whitfield

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  1. T. T. Andreassen
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  2. G. E. Willick
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  3. P. Morley
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  4. J. F. Whitfield
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Correspondence to T. T. Andreassen.

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Andreassen, T., Willick, G., Morley, P. et al. Treatment with Parathyroid Hormone hPTH(1-34), hPTH(1-31), and Monocyclic hPTH(1-31) Enhances Fracture Strength and Callus Amount After Withdrawal Fracture Strength and Callus Mechanical Quality Continue to Increase. Calcif Tissue Int 74, 351–356 (2004). https://doi.org/10.1007/s00223-003-0093-6

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